Quantum Cluster Variables via Serre Polynomials

For skew-symmetric acyclic quantum cluster algebras, we express the quantum $F$-polynomials and the quantum cluster monomials in terms of Serre polynomials of quiver Grassmannians of rigid modules. As byproducts, we obtain the existence of counting polynomials for these varieties and the positivity conjecture with respect to acyclic seeds. These results complete previous work by Caldero and Reineke and confirm a recent conjecture by Rupel.Comment: minor corrections, reference added, example 4.3 added, 38 page

Nearly Morita equivalences and rigid objects

If T and T′ are two cluster-tilting objects of an acyclic cluster category related by a mutation, their endomorphism algebras are nearly-Morita equivalent (Buan et al., Cluster-tilted algebras, Trans. Amer. Math. Soc. 359(1) (2007), 323–332 (electronic)), that is, their module categories are equivalent “up to a simple module”. This result has been generalised by D. Yang, using a result of Plamondon, to any simple mutation of maximal rigid objects in a 2-Calabi–Yau triangulated category. In this paper, we investigate the more general case of any mutation of a (non-necessarily maximal) rigid object in a triangulated category with a Serre functor. In that setup, the endomorphism algebras might not be nearly-Morita equivalent and we obtain a weaker property that we call pseudo-Morita equivalence. Inspired by Buan and Marsh (From triangulated categories to module categories via localization II: calculus of fractions, J. Lond. Math. Soc. (2) 86(1) (2012), 152–170; From triangulated categories to module categories via localisation, Trans. Amer. Math. Soc. 365(6) (2013), 2845–2861), we also describe our result in terms of localizations

Herpes Simplex Virus Type 2 Triggers Reactivation of Kaposi's Sarcoma-Associated Herpesvirus from Latency and Collaborates with HIV-1 Tat

Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy

Progress with retroviral gene vectors

Retroviral vectors have become a standard tool for gene transfer technology. Compared with other gene transfer systems, retroviral vectors have several advantages, including their ability to transduce a variety of cell types, to integrate efficiently into the genomic DNA of the recipient cells and to express the transduced gene at high levels. The relatively well understood biology of retroviruses has made possible the development of packaging cell lines which provide in trans all the viral proteins required for viral particle formation. The design of different types of packaging cells has evolved to reduce the possibility of helper virus production. The host range of retroviruses has been expanded by pseudotyping the vectors with heterologous viral glycoproteins and receptor-specific ligands. The development of lentivirus vectors has allowed efficient gene transfer to quiescent cells. This review describes different strategies adopted for developing vectors to be used in gene therapy applications

Identification of alpha-Helices from Low Resolution Protein Density Maps

This paper presents a novel methodology to analyze low resolution (e.g., 6A to 10A) protein density map, that can be obtained through electron cryomicroscopy. At such resolutions, it is often not possible to recognize the backbone chain of the protein, but it is possible to identify individual structural elements (e.g., alpha-helices and beta-sheets). The methodology proposed in this paper performs gradients analysis to recognize volumes in the density map and to classify them. In particular, the focus is on the reliable identification of alpha-helices. The methodology has been implemented in a tool, called Helix Tracer, and successfully tested with simulated structures, modeled from the Protein Data Bank at 10A resolution. The results of the study have been compared with the only other known tool with similar capabilities (Helixhunter), denoting significant improvements in recognition and precision